Browsing by Author "Cordova, Miguel"
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- ItemIn vivo imaging characterization of basal cell carcinoma and cutaneous response to high-dose ionizing radiation therapy: A prospective study of reflectance confocal microscopy, dermoscopy, and ultrasonography(2021) Navarrete-Dechent, Cristian; Cordova, Miguel; Liopyris, Konstantinos; Aleissa, Saud; Rajadhyaksha, Milind; Cohen, Gil'ad; Marghoob, Ashfaq A.; Rossi, Anthony M.; Barker, Christopher A.Background: Radiation therapy (RT) is a treatment option for select skin cancers. The histologic effects of RT on normal skin or skin cancers are not well characterized. Dermoscopy, high-frequency ultrasonography (HFUS), and reflectance confocal microscopy (RCM) are noninvasive imaging modalities that may help characterize RT response.
- ItemIn vivo optical imaging-guided targeted sampling for precise diagnosis and molecular pathology(2021) Sahu, Aditi; Oh, Yuna; Peterson, Gary; Cordova, Miguel; Navarrete-Dechent, Cristian; Gill, Melissa; Alessi-Fox, Christi; Gonzalez, Salvador; Phillips, William; Wilson, Steven; Afzalneia, Reza; Rose, Raven; Mohsere, Abu-Akeel; Bello, Danielle; Marghoob, Ashfaq; Rossi, Anthony; Wolchok, Jedd D.; Merghoub, Taha; Rotemberg, Veronica; Chen, Chih-Shan Jason; Rajadhyaksha, MilindConventional tissue sampling can lead to misdiagnoses and repeated biopsies. Additionally, tissue processed for histopathology suffers from poor nucleic acid quality and/or quantity for downstream molecular profiling. Targeted micro-sampling of tissue can ensure accurate diagnosis and molecular profiling in the presence of spatial heterogeneity, especially in tumors, and facilitate acquisition of fresh tissue for molecular analysis. In this study, we explored the feasibility of performing 1-2 mm precision biopsies guided by high-resolution reflectance confocal microscopy (RCM) and optical coherence tomography (OCT), and reflective metallic grids for accurate spatial targeting. Accurate sampling was confirmed with either histopathology or molecular profiling through next generation sequencing (NGS) in 9 skin cancers in 7 patients. Imaging-guided 1-2 mm biopsies enabled spatial targeting for in vivo diagnosis, feature correlation and depth assessment, which were confirmed with histopathology. In vivo 1-mm targeted biopsies achieved adequate quantity and high quality of DNA for next-generation sequencing. Subsequent mutational profiling was confirmed on 1 melanoma in situ and 2 invasive melanomas, using a 505-gene mutational panel called Memorial Sloan Kettering-Integrated mutational profiling of actionable cancer targets (MSK-IMPACT). Differential mutational landscapes, in terms of number and types of mutations, were found between invasive and in situ melanomas in a single patient. Our findings demonstrate feasibility of accurate sampling of regions of interest for downstream histopathological diagnoses and molecular pathology in both in vivo and ex vivo settings with broad diagnostic, therapeutic and research potential in cutaneous diseases accessible by RCM-OCT imaging.
- ItemIn vivo tumor immune microenvironment phenotypes correlate with inflammation and vasculature to predict immunotherapy response(2022) Sahu, Aditi; Kose, Kivanc; Kraehenbuehl, Lukas; Byers, Candice; Holland, Aliya; Tembo, Teguru; Santella, Anthony; Alfonso, Anabel; Li, Madison; Cordova, Miguel; Gill, Melissa; Fox, Christi; Gonzalez, Salvador; Kumar, Piyush; Wang, Amber Weiching; Kurtansky, Nicholas; Chandrani, Pratik; Yin, Shen; Mehta, Paras; Navarrete-Dechent, Cristian; Peterson, Gary; King, Kimeil; Dusza, Stephen; Yang, Ning; Liu, Shuaitong; Phillips, William; Guitera, Pascale; Rossi, Anthony; Halpern, Allan; Deng, Liang; Pulitzer, Melissa; Marghoob, Ashfaq; Chen, Chih-Shan Jason; Merghoub, Taha; Rajadhyaksha, MilindResponse to immunotherapies can be variable and unpredictable. Pathology-based phenotyping of tumors into 'hot' and 'cold' is static, relying solely on T-cell infiltration in single-time single-site biopsies, resulting in suboptimal treatment response prediction. Dynamic vascular events (tumor angiogenesis, leukocyte trafficking) within tumor immune microenvironment (TiME) also influence anti-tumor immunity and treatment response. Here, we report dynamic cellular-level TiME phenotyping in vivo that combines inflammation profiles with vascular features through non-invasive reflectance confocal microscopic imaging. In skin cancer patients, we demonstrate three main TiME phenotypes that correlate with gene and protein expression, and response to toll-like receptor agonist immune-therapy. Notably, phenotypes with high inflammation associate with immunostimulatory signatures and those with high vasculature with angiogenic and endothelial anergy signatures. Moreover, phenotypes with high inflammation and low vasculature demonstrate the best treatment response. This non-invasive in vivo phenotyping approach integrating dynamic vasculature with inflammation serves as a reliable predictor of response to topical immune-therapy in patients.
- ItemLentigo maligna melanoma mapping using reflectance confocal microscopy correlates with staged excision: A prospective study(2023) Navarrete-Dechent, Cristian; Cordova, Miguel; Aleissa, Saud; Liopyris, Konstantinos; Dusza, Stephen W.; Kose, Kivanc; Busam, Klaus J.; Hollman, Travis; Lezcano, Cecilia; Pulitzer, Melissa; Chen, Chih-Shan J.; Lee, Erica H.; Rossi, Anthony M.; Nehal, Kishwer S.Background: Lentigo maligna/lentigo maligna melanoma (LM/LMM) can present with subclinical extension that may be difficult to define preoperatively and lead to incomplete excision and potential recurrence. Preliminarily studies have used reflectance confocal microscopy (RCM) to assess LM/LMM margins.
- ItemPerifollicular linear projections: A dermatoscopic criterion for the diagnosis of lentigo maligna on the face(2024) Navarrete-Dechent, Cristian; Jaimes, Natalia; Dusza, Stephen W.; Liopyris, Konstantinos; Marchetti, Michael A.; Cordova, Miguel; Oliviero, Margaret; Villaseca, Miguel A.; Pulitzer, Melissa; Busam, Klaus J.; Rossi, Anthony M.; Rabinovitz, Harold S.; Nehal, Kishwer S.; Scope, Alon; Marghoob, Ashfaq A.Background: Lentigo maligna (LM) can mimic benign, flat, pigmented lesions and can be challenging to diagnose. Objective: To describe a new dermatoscopic feature termed "perifollicular linear projections (PLP)"as a diagnostic criterion for LM on the face. Methods: Retrospective study on reflectance confocal microscopy and dermatoscopy images of flat facial pigmented lesions originating from 2 databases. PLP were defined as short, linear, pigmented projections emanating from hair follicles. Dermatoscopy readers were blinded to the final histopathologic diagnosis. Results: From 83 consecutive LMs, 21/83 (25.3%) displayed "bulging of hair follicles"on reflectance confocal microscopy and 18 of these 21 (85.7%), displayed PLP on dermatoscopy. From a database of 2873 consecutively imaged and biopsied lesions, 252 flat-pigmented facial lesions were included. PLP was seen in 47/76 melanomas (61.8%), compared with 7/176 lesions (3.9%) with other diagnosis (P \ .001). The sensitivity was 61.8% (95% CI, 49.9%-72.7%), specificity 96.0% (95% CI, 92.9%-98.4%). PLP was independently associated with LM diagnosis on multivariate analysis (OR 26.1 [95% CI, 9.6%-71.0]). Limitations: Retrospective study. Conclusion: PLP is a newly described dermatoscopic criterion that may add specificity and sensitivity to the early diagnosis of LM located on the face. We postulate that PLP constitutes an intermediary step in the LM progression model. ( J Am Acad Dermatol 2024;90:52-7.)
- ItemTreatment of Extramammary Paget Disease and the Role of Reflectance Confocal Microscopy: A Prospective Study(2021) Navarrete-Dechent, Cristian; Aleissa, Saud; Cordova, Miguel; Hibler, Brian P.; Erlendsson, Andres M.; Polansky, Max; Cordova, Frank; Lee, Erica H.; Busam, Klaus J.; Hollmann, Travis; Lezcano, Cecilia; Moy, Andrea; Pulitzer, Melissa; Leitao, Mario M., Jr.; Rossi, Anthony M.BACKGROUND Extramammary Paget disease (EMPD) poses treatment challenges. Invasive and noninvasive treatment modalities exist with variable success reported. Reflectance confocal microscopy (RCM) is emerging as an adjuvant diagnostic tool. OBJECTIVE To evaluate the treatment of EMPD patients and the role of RCM. METHODS Prospective study. Demographic and tumor characteristics were recorded. Handheld-RCM was performed and correlated with histology. Treatment, clearance, pathology, and follow-up were all recorded. RESULTS Thirty-six EMPD lesions in 33 patients were included. Mean age was 71.7 years, and 23 were men. Mean number of surgical stages needed to clear margins was 1.9 (SD, 0.9; 1.0-3.0 stages), and mean margin needed to clear was 1.8 cm. Reflectance confocal microscopy correlated well with scouting punch biopsies (kappa, 0.93; p < .001). Disruption of the dermoepidermal junction was associated with invasive EMPD versus in situ (83.3% vs 25.9%) on histology (p = .01). Limitations Relatively small sample size. CONCLUSION Extramammary Paget disease is challenging, and lesion demarcation is of the utmost importance. Using a staged surgical excision approach, the mean margins needed were 1.8 cm, less than previously reported. Nonsurgical modalities, including radiation therapy, imiquimod, or photodynamic therapy can be considered if surgery is not pursued. Reflectance confocal microscopy is a valuable noninvasive imaging modality for the management of EMPD.